Non-invasive approaches in the diagnosis of acute rejection in kidney transplant recipients, part II: omics analyses of urine and blood samples

Abstract

Kidney transplantation (KTx) represents the best available treatment for patients with end-stage renal disease. Still, the full benefits of KTx are undermined by acute rejection (AR). The diagnosis of AR ultimately relies on transplant needle biopsy. However, such an invasive procedure is associated with a significant risk of complications and is limited by sampling error and interobserver variability. In the present review, we summarize the current literature about non-invasive approaches for the diagnosis of AR in kidney transplant recipients (KTRs), including in vivo imaging, gene-expression profiling and omics analyses of blood and urine samples. Most imaging techniques, such as contrast-enhanced ultrasound and magnetic resonance, exploit the fact that blood flow is significantly lowered in case of AR-induced inflammation. In addition, AR-associated recruitment of activated leucocytes may be detectable by 18F-fluorodeoxyglucose positron emission tomography. In parallel, urine biomarkers, including CXCL9/CXCL10 or a three-gene signature of CD3ε, CXCL10 and 18S RNA levels, have been identified. None of these approaches has yet been adopted in the clinical follow-up of KTRs, but standardization of analysis procedures may help assess reproducibility and comparative diagnostic yield in large, prospective, multicentre trials.

Urinary CCL2 and CXCL10 chemokines as potential biomarkers of ongoing pathological processes in kidney allograft: association with BK virus nephropathy

“…The utility of different urinary and serum biomarkers, including chemokines CCL2 and CXCL10, has been broadly analyzed. 33,34 In our study, the CCL2:Cr ratio was highly elevated and corresponded with pathological lesions in the kidney graft. It correlated with renal function parameters such as serum creatinine and eGFR levels, but not with albuminuria.…”

Observer variability in the assessment of renal 18F-FDG uptake in kidney transplant recipients

“…Still, it is associated with a substantial risk of complications, such as hemorrhage or infection 12 . Thus, non-invasive approaches have been developed over the past decades in order to help clinicians avoid potential side effects of TNB [13][14][15] . Particularly, promising preclinical and clinical observations have been reported on the role of 18 F-fluorodeoxyglucose ( 18 F-FDG) positron-emission tomography coupled with computed tomography (PET/CT) in kidney allograft AR, in both diagnosis and therapeutic monitoring [16][17][18] .…”

Diagnosis, Treatment, and Outcomes of Antibody-Mediated Rejection in Kidney Transplantation

“…The ability to identify AMR, and perhaps even characterize AMR phenotypes based on gene expression profiles in biopsy tissue [128,129] should allow a clearer determination of AMR severity and ultimately help guide therapy. The identification of serum and/or urinary biomarkers [130][131][132][133] should enable better surveillance, earlier diagnosis of AMR, and prompt treatment to prevent irreversible tissue injury. Ultimately, optimizing the diagnosis and treatment of AMR will lead to greater graft longevity and thus, better utilization of this vastly limited resource.…”